OVERALL PROJECT OBJECTIVES: This research proposal is designed to capitalize on recent advances of knowledge of immunoglobulin structure. This should allow better definition of immunoglobulin regulation, specific biological functions and, hopefully, genetic regulation. The specific aims of this proposal are the following: 1) Completion of the total primary structure of J-chain. 2) Definition of disulfide linkages in J-chain and determination of sites of J-H linkages. 3) Examination of molecular parameters necessary for the C micron 4 domain of IgM to activate Cl. 4) Examination of the structure of the membrane component of mouse lymphocyte (TL) as a possible primordial immunoglobulin-like molecule. It is anticipated that these studies will lead to new insights into the structure and function relationships of immunoglobulin molecules. We further anticipate that this knowledge can be adapted for pharmacodynamic application to therapy and management of inflammatory diseases or diseases of deficiency in function of the immune system. BIBLIOGRAPHIC REFERENCES: Mole, J.E., Bhown, A.S. and Bennett, J.C. Sequence Analysis of Human J Chain. Amino Terminal Location of a Disulfide Bond Linking the Immunoglobulin Heavy Chain. Biochem. Biophys. Res. Comm. 73:92 (1976). Mole, J.E., Bhown, A.S. and Bennett, J.C. Structural Analysis of the Peptides Derived from Specific Acid-catalyzed Hydrolysis at Aspartyl-Prolyl Peptide Bonds in Human J Chain. J. Immunol. 118:67 (1977).